Standard methods for generating recombinant DNA constructs are sequence-dependent in that they rely on the use of restriction enzymes to cut DNA into specific fragments, which can then be rejoined in new combinations. Examples of engineered fusion proteins in the recent literature include: a ligand fused to a toxin to direct it to a specific cell type (Kim et al., 1988), a set of chimeric molecules used to map a determinant (Landau et al., 1988), and two peptide hormones fused to give a product with activities of both (Feng et al., 1988). Various engineering strategies were employed to generate these products, but each has its limitations. In one case, sequences from a multiple cloning site were used to join the two fragments, and the resultant protein thus contained irrelevant amino acids (Kim et al., 1988). In another example, silent restriction sites were introduced into the molecules to be recombined (Landau et al., 1988). This approach is limited by the requirement that the nucleic acid changes generating the restriction sites must not introduce undesired amino acid changes. In the third example, double-stranded synthetic oligos containing the desired fusion sequence were used to join the fragments (Feng et al., 1988). Even this approach, however, is dependent on the occurrence of restriction sites near enough to the fusion site to be included in a synthetic oligo.